This review discusses the application of nano-drug delivery systems based on natural products, highlighting their potential in overcoming the limitations of natural products such as poor solubility, limited biological distribution, and rapid metabolic clearance. Nano-drug delivery systems offer advantages such as enhanced targeting capabilities, sustained and controlled release, and improved bioavailability. The review covers three main aspects: connecting targeting warheads, self-assembly, and co-delivery. It provides detailed examples of nano-drug delivery systems for terpenoids, flavonoids, polyphenols, and alkaloids, including triptolide, ginsenosides, gambogic acid, baicalin, resveratrol, curcumin, paclitaxel, ursolic acid, rhein, and berberine. The review also explores self-assembled nano-drug delivery systems, emphasizing the use of peptides and metal-coordinated polyphenols. These systems demonstrate significant improvements in drug efficacy, safety, and targeted delivery, making them promising candidates for clinical applications. The challenges and future directions in the clinical translation of nano-drugs are also discussed.This review discusses the application of nano-drug delivery systems based on natural products, highlighting their potential in overcoming the limitations of natural products such as poor solubility, limited biological distribution, and rapid metabolic clearance. Nano-drug delivery systems offer advantages such as enhanced targeting capabilities, sustained and controlled release, and improved bioavailability. The review covers three main aspects: connecting targeting warheads, self-assembly, and co-delivery. It provides detailed examples of nano-drug delivery systems for terpenoids, flavonoids, polyphenols, and alkaloids, including triptolide, ginsenosides, gambogic acid, baicalin, resveratrol, curcumin, paclitaxel, ursolic acid, rhein, and berberine. The review also explores self-assembled nano-drug delivery systems, emphasizing the use of peptides and metal-coordinated polyphenols. These systems demonstrate significant improvements in drug efficacy, safety, and targeted delivery, making them promising candidates for clinical applications. The challenges and future directions in the clinical translation of nano-drugs are also discussed.